Glutamate receptors that are selective for N-methyl-D-aspartate (NMDA) are a major class of neurotransmitter receptors that are essential for brain function. Abnormal regulation and dysfunction of NMDA receptors have been associated with many brain disorders including epilepsy, autism, stroke, and schizophrenia. NMDA receptors play a critical role in the development of neuronal circuits, but the underlying mechanisms are poorly understood. In this proposal we focus on the role of NMDA receptors in the maturation of neurons and synapses during early life. Specifically, we will address two important questions: 1) What is the role of NMDA receptors in the development of function and morphology of neurons; and 2) What is the role of NMDA receptor alternative splicing in the maturation of excitatory synapses and in the regulation of network excitability. The answers to these questions have broad implications for brain disorders. We use a multidisciplinary approach to address these questions, taking advantage of genetic manipulation, electrophysiology, anatomy, and molecular analyses in the mouse.